Marina Gorbatyuk headshot.

Associate Professor

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(205) 943-6762
Office location: VH 443

Teaching/research interests: VS 112 Physiology of the Eye; VS 745 Biology and Pathology of the Posterior Segment

Office hours: By appointment

Education:  

  • PhD, Institute of Biotechnology, Russia, Biotechnology

I grew up in Russia and received my Ph.D. from the Russian Institute of Biotechnology in Moscow. In 1998, I moved to the United States and accepted a postdoctoral position in Dr. Al Lewin’s laboratory at the University of Florida, Gainesville. During my postdoctoral training, I investigated the mechanism of retinal pathogenesis associated with the expression of misfolded rhodopsin proteins. I have been working on designing a gene therapy targeting different mutations within the rhodopsin gene in rodent and dog models of retinal degenerations. My keen interest in the science lay in the field of retinal cell biology and cellular molecular signaling, activated upon retinal degeneration. I have been looking for neuroprotective strategies that rescue degenerating photoreceptors. Thus, I have begun to study the unfolded protein response (UPR) activated in photoreceptors expressing misfolded proteins and realize that the apoptotic photoreceptor cell death could be delayed by reprograming chronically activated UPR. I have developed a program aimed at targeting the activated UPR in degenerating retina, sponsored by the National Eye Institute. My first appointment as an assistant professor was with the North Texas University Health Science Center where I continued working on the mechanism of retinal degeneration in varied animal models. In 2012, I moved to Birmingham and joined the faculty of the School of Optometry at the University of Alabama at Birmingham as an associate professor where I continue my work on vision restoration.

Research interests:

Research in my laboratory focuses on the biochemistry and molecular biology of degenerating photoreceptors. Interestingly, varied models of retinal degeneration expressing misfolded proteins in photoreceptors are characterized by chronic activation of the UPR. Mammalian cells activate UPR in response to various internal and external cellular stimuli, disturbing the balance in the endoplasmic reticulum (ER). These stimuli include misfolded proteins, glucose deprivation, calcium dysfunction, inflammation, redox potential changes, and mechanical stress. This activation results in an adjustment of the ER’s capacity to assist protein in the folding activation of the ER-associated degradation (ERAD) pathway for degradation of abnormal proteins and re-establishment of cellular homeostasis. However, a stimulus of long-lasting duration may cause chronic ER stress. For example, persistent expression of misfolded rhodopsin in photoreceptors activates chronic activation of ER stress response. In this scenario, cells experience a “’pathological” UPR that triggers programmed cell death, usually through sustained activation of the PERK UPR arm and pro-apoptotic components of cellular signaling. Recognition of a molecular switch operating between photoreceptor cell life and death decisions is a major focus of my scientific program.

Chronic UPR activation triggers multiple aberrant cellular signaling, leading to apoptotic cell death. One of such programs is translational attenuation that, under physiological conditions, is temporally initiated until the ER capacity to handle misfolded proteins is not restored. Agreeing with chronic UPR activation, observed translational attenuation proposes that the rate of protein synthesis in the mice with retinal degeneration is inhibited. However, whether translational attenuation in these mice is a pro-survival program that is still attempting to restore cellular homeostasis in photoreceptor cells or a consequence of pathological UPR leading to apoptosis is still unclear and perhaps will be revealed by our lab. Members of my lab work with rat and mouse models of retinal degeneration and use functional, imaging, and molecular biological techniques to examine retinal pathogenesis and vision loss in animals.

Recent courses taught:

  • VS 112 Physiology of the eye
  • VS 745 Biology and Pathology of the Posterior Segment

Select publications:

  • Gorbatyuk, M.S., Knox, T., LaVail, M.M., Gorbatyuk, O.S., Noorwez,S.M., Hauswirth, W.W., Lin, JH, Muzyczka, N. and Lewin, AS “Restoration of Visual Function in P23H Rhodopsin Transgenic Rats by Gene Delivery of BiP/Grp78”. Proc Natl Acad Sci USA., 107:5961-6, 2010.
  • Gorbatyuk M, Shabashvili A., Chen W, Meyers G, Sullivan L., Lin J., Lewin A., Muzyczka N. and Gorbatyuk O. “Glucose regulated protein 78 (GRP78/BiP) meliorates alpha-synuclein (α-syn) neurotoxicity in a rat model of Parkinson disease". Mol Ther., 7:1327-37, 2012.
  • Shreyasi Choudhury, Yogesh Bhootada and Marina Gorbatyuk “Caspase-7 Ablation Modulates UPR, Reprograms TRAF2-JNK Apoptosis and Protects T17M Rhodopsin Mice from Severe Retinal Degeneration”. Cell Death Dis., 7;4:e528. doi: 10.1038/cddis.2013.34, 2013.
  • Marina Gorbatyuk and Oleg Gorbatyuk “The Molecular Chaperone GRP78/BiP as a Therapeutic Target for Neurodegenerative Disorders”. Review. Jour of Gen Syndr & Gen The., 4(2), 2013.
  • Xiaoqin Wang, Guibo Wang, Mansi Kunte, Vishal Shinde and Marina Gorbatyuk. “ Modulation of Angiogenesis by Genetic Manipulation of ATF4 in Mouse Model of Oxygen Induced Retinopathy”. Invest Ophthalmol Vis Sci., 54(9):5995-6002. doi: 10.1167/iovs.13-12117, 2013.
  • Shreyasi Choudhury, Sonali Nashine, Yogesh Bhootada, Mansi Motiwale Kunte, Oleg Gorbatyuk, Alfred S. Lewin, Marina Gorbatyuk “Modulation of the rate of retinal degeneration in T17M RHO mice by reprogramming the Unfolded Protein Response” in Retinal Degenerative Diseases. Adv Exp Med Biol., doi: 10.1007/978-1-4614-3209-8-58, Vol.801, 2014.
  • Tapasi Rana, Vishal Shinde, Christopher Starr, Artem Kruglov, Evan Boitet, Pravallika Kotla, Sergei Zolotukhin, Alecia Gross and Marina Gorbatyuk “An activated unfolded protein response promotes retinal degeneration and triggers an inflammatory response in the mouse retina” Cell Death and Disease (2014) 5, e1578; doi:10.1038/cddis.2014.
  • Austin R.Lenox, Yogesh Bhootada, Oleg Gorbatyuk, Roderick Fullard, and Marina Gorbatyuk. Unfolded protein response is activated in aged retinas. Neuroscience Letter. Volume 609, 2015.
  • Vishal Shinde, Pravallika Kotla, Christina Strang, and Marina Gorbatyuk. Unfolded protein response-induced dysregulation of calcium homeostasis promotes retinal degeneration in rat models of autosomal dominant retinitis pigmentosa. Cell Death and Disease; 7, e2085, 2016.

Academic distinctions and professional societies:  

  • Association for Research in Vision and Ophthalmology
  • International Society for Eye Research